This investigation will be conducted in order to examine the hypotheses that (1) repeated exposure to morphine induces in cells within the central nervous system the formation of a low molecular weight peptide capable of altering subsequent cellular response to opiate congeners and (2) the administration of brain extracts containing this peptide to naive animals can result in the transfer of opiate tolerance and physical dependence in such recipients. Specifically, we intend to demonstrate the generality of the transfer of morphine tolerance and physical dependence from donor rats to naive mice using three behavioral measures of morphine's action, i.e., analgesia, stereotyped locomotor activity, and central excitation, as well as the phenomenon of naloxone precipitated withdrawal. As a result of these experiments, we plan to establish a sensitive bio-assay for detecting the presence of the transfer factor and conduct studies directed toward determining the subcellular and anatomical distribution of this substance. Additional effort will be made to enhance our understanding of the mechanism(s) by which such transfer is effected by examining the ability of this tissue factor to directly antagonize selected actions of morphine in vitro and in vivo and by evaluating the influence of protein synthesis inhibition on the transfer phenomenon. It is anticipated that these studies will provide unequivocal evidence necessary to support or reject the concept of the chemical transfer of opiate tolerance and/or dependence. Moreover, the information gained should enhance our understanding of the molecular mechanisms responsible for these phenomena and thus could be of considerable social and therapeutic value.